Cardiovascular diseases are the leading cause of mortality worldwide and are projected to cause more than 20 million deaths per year by 2030. Cardioembolic stroke is one of the most devastating consequences of cardiac diseases, both in terms of mortality and disability. In embolic strokes, a blood clot or other material travels to the brain from another site and occludes a blood vessel, thereby depriving the brain of the needed blood flow (and associated oxygen and glucose supplies); this results in the death of the cells that are usually supplied by this blood flow. The most common source for these emboli is the heart. Blood clots, otherwise known as thrombi, can form in patients with atrial fibrillation, heart valves, artificial materials (e.g., artificial hearts, vascular stents, and the like), or significant heart disease.
Three major mechanisms promote intracardiac thrombosis and embolism in cardiac diseases. First, endocardial injury, due to surgery, chronic stretch or ischemic necrosis, activates clot formation by exposing pro-coagulation factors of the basal membrane. Additionally, cardiac diseases are frequently associated with chronic inflammation, and increased catecholamine and inflammatory cytokine levels, which induce a systemic hypercoagulable state. Finally, blood flow stagnation triggers the activation of the coagulation system. These three predisposing factors are classically known as “Virchow's triad” (Lowe 2003). Diseases such as atrial fibrillation, myocardial infarction, dilated and hypertrophic cardiomyopathies are well-established conditions that increase the risk of cardiac embolisms by a combination of these three mechanisms.
Anticoagulation therapy has proven to be effective for decreasing the risk of cardioembolic events. However, the benefits of anticoagulation are frequently neutralized by the increased hemorrhagic risk associated with this therapy (Massie et al 2009). In fact, most clinical trials assessing the efficacy of primary prevention of anticoagulation therapy in non-atrial fibrillation (non-AF) cardioembolic diseases have been negative or neutral (Bakalli et al 2013, Homma et al 2012). These trials have been based on clinical risk factors and demographic variables, because precision individualized risk assessment methods are lacking. We hypothesize that imaging-based biomarkers are particularly well suited for this purpose.
Mechanical left-ventricular-assisted-devices (LVADS) are being used as temporary and destination therapies in an increasing number of patients with end-stage heart failure (HF) (Toeg et al 2014). However, intraventricular thrombosis is a well-recognized complication of LVADs and may lead to device malfunction and embolism. A quantitative and individualized topologic assessment of the chamber regions at particular risk for thrombus development may help to define the ideal locations for the insertion of the LVAD cannulas on a patient-specific basis and, to optimize the device operating settings.
Flow in the heart involves complex fluid transport and mixing processes (Bermejo et al 2015). Intracardiac transport and mixing depends on convoluted trajectories of flow inside the chambers (Kilner et al 2000, Wigstrom et al 1999, Zhang et al 2012) as well as on the dynamical interactions between incoming flow and residual flow from preceding cycles (Bolger et al 2007). In the healthy heart, these phenomena result in a small residual volume with no associated blood stasis. However, intraventricular flow patterns are significantly altered by disease (Bermejo et al 2014, Eriksson et al 2013, Hong et al 2008, Rodriguez Munoz et al 2013). How these disturbed flow dynamics may lead to increased blood stasis is only beginning to be understood (Eriksson et al 2013, Hendabadi et al 2013).
Currently, there are no tools capable of a high-throughput measurement of flow stasis in the clinical setting. It would be desirable, therefore, to provide methods capable of a high-throughput measurement of flow stasis in the clinical setting to inform treatment options for patients at risk for thrombus formation.